Septanoses, seven membered ring carbohydrates, are
synthetic analogs of pyranoses where an additional carbon atom has been added
to the ring. Septanosides have shown activity as ligands of lectins as well as
substrates for glycosidase enzymes. In the course of synthesizing carbohydrate
based oxepines which are themselves useful starting materials for oligosaccharides,
we discovered the formation of 1,4-anhydroseptanoses. The synthesis of the
precursors of cyclization started with an addition of vinyl magnesium bromide
onto pyranose lactols followed by ozonolysis. The hydroxy aldehyde products of
this two-step sequence were trapped as their cyclic acetals via acetylation,
giving 1,2-di-O-acetyl-3,4,5,6-tetra-O-benzyl septanoses. The 1,2-di-O-acetates
were converted to their anomeric halides using HBr in acetic acid or
iodotrimethylsilane followed by in situ intramolecular attack of a benzyl ether
oxygen onto the anomeric carbon then gave rise to the new 1,4-anhydrosugars.
Yields of the respective 1,4-anhydroseptanose analogs were moderate to high and
the regioselectivity of the cyclization product was confirmed by 2D NMR
techniques as well as X-ray crystallography. The transformation is relatively
general and was extended to septanoses derived from mannose, xylose and
galactose. A regioselective conversion of 1,4-anydro species to septanose
glycosides in preference to furanoses was also demonstrated proving that these
are valuable intermediates for oligomerization of septanose carbohydrates. We
posit that the newly discovered 1,4-anhydroseptanoses can serve as effective
starting materials for septanose-based conjugates. Optimization of the reaction
conditions and scope of the nucleophiles for the selective opening
1,4-anhydrosugars to prove the utility of this method is to be studied in
future.

T7

Time series lipidomics analysis of green microalgae under nutrient stress

The utilization of fossil fuels as energy sources
leads to carbon dioxide and other gas emissions that contribute to global
warming. As such, methods that can replace these with alternative, clean and
renewable energy sources are of great interest. Many plants produce lipids such
as triacylglycerols (TAGs) which are precursor molecules for biodiesel
production. Microalgae present an attractive alternative since they have a
higher oil yield than other plants and when grown under certain conditions they
accumulate lipids and can be grown on water and therefore do not compete with
agricultural land. The aim of this study is to analyze the changes in
lipid-derived value added metabolites produced by microalgae under different
growth conditions to gain information at the molecular level to understand the
metabolic processes that accompany these changes. We chose a highly-adaptable,
oleaginous, non-model microalgae, Ettlia oleaobundans. We developed a MS-based
metabolomics method to analyze the changes in metabolites under different
growth conditions using LC-Q-ToF, under nitrogen and phosphorous replete (N+,
P+) and deplete (N-, P-) conditions. Untargeted and targeted analysis of the
changes in metabolite composition highlighted the accumulation of TAGs and
depletion of chlorophylls and certain structural lipids for photosynthesis
under nutrient deprived conditions. In addition, we found a correlation between
the changes in certain plant lipids under N- and P- conditions, suggesting that
cells start utilizing different energy sources as an alternative under these conditions.
Using this information, we are working on identifying lipid-related pathways
that derive the growth and lipid production as a response to nutrient stress.

Microplastics are a growing interest in the world
of environmental science and are becoming more well-known as a component of
plastic pollution. As the largest source of surface fresh water in the world,
the Great Lakes are an important place to study the potential of these
particles becoming pollutants and a transport medium of further pollution,
specifically if they are also adsorbing potentially toxic chemicals to their
surfaces. The goal of this research is to use surface analytical techniques
like Fourier-transform infrared spectroscopy (FTIR) and time-of-flight
secondary ion mass spectrometry (ToF-SIMS) to characterize and examine the
surfaces of microplastics taken from the Great Lakes for evidence of adsorbed
chemical pollutants. Based on the data collected from our experiments and
previous studies on the chemical relationships between plastics and pollutants
in water, we concluded that chemicals such as Silicones(TM) and fluorocarbons
are adsorbing to the surfaces of these microplastics due to the hydrophobicity
of both the plastics and the chemicals of interest.

T9

Toward Chemical Assembly of Split Toxins for Targeted Cancer Therapy

Hsuan-yi Wu, Yulin Tian and Qing Lin

University at Buffalo,
Department of Chemistry

Diphtheria toxin (DT) and Pseudomonas aeruginosa
exotoxin A (PE) are two bacterial toxins that have been employed in the design
of the immunotoxin-based cancer therapies. These two toxins exhibit potent cell
killing through enzymatic inactivation of the elongation factor 2 (EF-2), an
indispensable protein component of the eukaryotic translational machinery. A
number of immunotoxins have entered into clinical trials for treatment of a
variety of cancers, including leukemia, breast cancer, and esophageal cancer.
The structure of bacterial toxins are comprised of a catalytic domain, a
translocation domain, and a receptor binding domain, though the order of
linkage of these three domains may vary. A drawback of current immunotoxins is
that due to their long half-lives in blood stream (usually two to three weeks),
they can be potentially taken up by normal cells, leading to serious side
effects. To overcome this problem, we hypothesized that the half-lives of
immunotoxins can be significantly attenuated if we chemically assemble the
immunotoxins selectively in cancer tissues in situ from the smaller protein
domains. In this talk, I will describe our preliminary work in recombinant
expression of the individual domains of the bacterial toxins, their conjugation
to prostate cancer-targeting ligands, and the evaluation of the cell-killing
activity of the cancer-targeted toxins in prostate cancer cell lines, PC3 and
LNCaP

T10

Quantitation of Stercobilin in the Fecal Material of Timothy Syndrome
Mice as a Putative Biomarker for Autism

Emily Sekera Troy D. Wood, Heather L Rudolph and Stephen Carro

University at Buffalo, Department of Chemistry

Autism Spectrum Disorders (ASD) is a general term
for a group of complex disorders that currently effect 1 out of every 68
children in the United States which has risen significantly since 2007 (up from
1 out of every 150 children). Previous research in our group showed the
depletion of an unknown in the urine of autistic children versus that of the
controls. Utilizing MS/MS and FT-ICR MS the peak was determined to be the
metabolite stercobilin. In this study, we utilize a highly-controlled animal
model using transgenic Timothy Syndrome (TS) mice to determine if stercobilin
is a viable biomarker for diagnosing autism. A method to create labelled
stercobilin isotopomers for quantitation by mass spectrometry was developed and
fine-tuned to test the fecal material from transgenic mice and their
littermates. In the progress of our studies, we recognized that a higher yield
of stercobilin than previously anticipated (based on stercobilin in urine) has
been attained from the excrement samples. Due to this, response factor (RF)
calculations were completed to determine the amount of spike that was necessary
to quantify the amount of stercobilin in all of our samples. From here we aim
to further evaluate the statistical significance of the depletion of
stercobilin in “autistic” mice as a potential approach to diagnosing autism.